1. Field of the Invention
The present invention relates to novel analogs of 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA), to processes for their production and to their use as anti-tumor agents for the inhibition of malignant tumors in mammals.
2. Description of the Prior Art
The m-AMSA analogs of the present invention in general have the basic structure and numbering system as shown below. ##STR2##
It should be understood that although the numbering system employed is that shown above, some of the prior art uses a reverse system and numbers the acridine nucleus from right to left instead of left to right.
Acridinylaminomethanesulfonanilide derivatives have been studied in recent years for anti-tumor activity. Various examples of both naturally occurring and semi-synthetic compounds of this class have been described in the literature. Illustrative of the more relevant publications are the following:
1. Numerous 4'-(9-acridinylamino)-methanesulfonanilide (AMSA) and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) analogs containing various substituted acridine nuclei are reported to have been investigated for anti-tumor activity in J. Med. Chem. 19,772,1124,1409 (1976).
AMSA and m-AMSA have the structural formulae: ##STR3##
2. It is disclosed in Drugs of the Future 5,277 (1980) and references therein that m-AMSA, (1, R.sup.1 .dbd.R.sup.2 .dbd.H) is a compound with a broad spectrum of experimental anti-tumor activity and has been under clinical evaluation in the treatment of a number of human tumors.
3. European Patent Application No. 0025705A1 discloses m-AMSA analogs having anti-tumor activity in animals of the formula ##STR4## in which: R.sup.1 represents CH.sub.3, CH.sub.2 CH.sub.3, or (CH.sub.2).sub.2 CH.sub.3 ;
R.sup.2 represents CONHR.sup.4, F, Cl, Br, I, CF.sub.3, NO.sub.2, NH.sub.2, CH.sub.3, OCH.sub.3, or NHCOCH.sub.3 ; and PA1 R.sup.3 represents CONHR.sup.4, H, CH.sub.3 or OCH.sub.3, with the proviso that at least one of R.sup.2 and R.sup.3 represents CONHR.sup.4 ; and PA1 R.sup.4 represents H, CH.sub.3, CH.sub.2 CH.sub.3, (CH.sub.2).sub.2 CH.sub.3, (CH.sub.2).sub.3 CH.sub.3 or CH.sub.2 CH(CH.sub.3).sub.2, each substituted or unsubstituted by one or more of the same of different substituents selected from hydroxyl, amine and amide functions, amine and amide being optionally substituted; and the acid additional salts thereof. PA1 R.sup.1 is Cl, Br, or CH.sub.3, and PA1 R.sup.2 is CH.sub.2 NHCH.sub.3, CH.sub.2 N(CHO)CH.sub.3 or CH.sub.2 NHCHO.